In this study, the newborn piglet model was used to assess theophylline absorption from various areas of the GI tract. 13 piglets, ages 9-14 days, had their intestines surgically exposed. Four segments of equal length (jejunum, ileum, right colon and left colon) were simultaneously perfused with a saline solution containing [3H]-polyethylene glycol 4000 to measure water shifts and theophylline at a total dose of 5 mg/kg, a typical neonatal dose. Absorption of theophylline, appearance in serum, and the effects of the drug on water and electrolyte movement in the intestinal segments were monitored. Serum concentrations of theophylline after an intravenous and oral dose were also studied in 2 piglets. The data showed excellent absorption of the drug from all intestinal segments studied (jejunum 0.97 +/- 0.16, ileum 0.7 +/- 0.13, right colon 0.7 +/- 0.13, and left colon 0.88 +/- 0.19 micrograms/cm/min), despite a concomitant secretion of sodium chloride and water. No statistical differences in absorptive capacity were seen among segments. The results suggest that as little as 100 cm of residual intestine could, theoretically, absorb a 5 mg dose of theophylline if presented slowly. These findings have ramifications for neonates who may receive theophylline orally or rectally.